Hu K F, Elvander M, Merza M, Akerblom L, Brandenburg A, Morein B
Department of Veterinary Microbiology, College of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala.
Clin Exp Immunol. 1998 Aug;113(2):235-43. doi: 10.1046/j.1365-2249.1998.00650.x.
ISCOM is an efficient mucosal delivery system for RSV envelope proteins as measured by antibody responses in respiratory tract secretions and in sera of mice following two intranasal (i.n.) administrations. Intranasally administered RSV ISCOMs induced high levels of IgA antibodies both in the upper respiratory tract and in the lungs. In the lungs, a prominent and long-lasting IgA response was recorded, which still persisted 22 weeks after the second i.n. immunization when the experiment ended. Subcutaneous (s.c.) immunization only induced low IgA titres in the upper respiratory tract and no measurable response to RSV was found in the lungs. Differences were also noticed in serum between the i.n. and s.c. modes of immunization. ISCOMs given intranasally induced earlier, higher and longer lasting IgM and IgG1 serum anti-RSV antibody responses than those induced by the s.c. mode of administration. A low serum IgE response was only detectable at 2 weeks after i.n. immunization with ISCOMs and after s.c. immunization with an inactivated virus, but no IgE response was detectable after s.c. injection of ISCOMs. The serum IgA response was more pronounced following s.c. injection of inactivated virus than after i.n. application of ISCOMs, and a clear-cut booster effect was obtained with a second immunization. Virtually no serum IgA response was detected after the s.c. administration of ISCOMs. In conclusion, the high immune responses induced by RSV ISCOMs in the respiratory tract and serum after i.n. administration indicate prominent mucosal delivery and adjuvant properties of the ISCOMs, warranting further studies.
通过两次鼻内给药后小鼠呼吸道分泌物和血清中的抗体反应测定,免疫刺激复合物(ISCOM)是一种用于呼吸道合胞病毒(RSV)包膜蛋白的高效黏膜递送系统。鼻内给药的RSV ISCOM在上呼吸道和肺部均诱导产生高水平的IgA抗体。在肺部,记录到显著且持久的IgA反应,在第二次鼻内免疫后22周实验结束时该反应仍然持续存在。皮下免疫仅在上呼吸道诱导产生低水平的IgA滴度,且在肺部未发现对RSV的可测量反应。在鼻内和皮下免疫方式之间,血清中也观察到差异。鼻内给予的ISCOM比皮下给药方式诱导产生更早、更高且更持久的血清抗RSV IgM和IgG1抗体反应。仅在鼻内给予ISCOM免疫后2周以及皮下注射灭活病毒后可检测到低水平的血清IgE反应,但皮下注射ISCOM后未检测到IgE反应。皮下注射灭活病毒后的血清IgA反应比鼻内给予ISCOM后更明显,且第二次免疫可获得明显的加强效应。皮下给予ISCOM后几乎未检测到血清IgA反应。总之,鼻内给药后RSV ISCOM在呼吸道和血清中诱导产生的高免疫反应表明ISCOM具有显著的黏膜递送和佐剂特性,值得进一步研究。